We determined the minimal folding domain for a construct of a recombinant form of the protein that had a MADS box DNA-binding domain as well as a MEF-2 myogenic domain using proteolysis and MALDI-MS. Showed that the N-terminal, susceptible to proteolysis in the absence of DNA, became highly resistant to proteolysis is the presence of Mef2C-specific DNA. The information was used to design new constructs of the protein for X-ray crystallographic studies.